Is the link between atrial fibrillation and obesity epicardial fat?

The epicardial fat pad image on chest x-rays was long regarded as nothing more than a barely  interesting incidental finding of no clinical importance. That no longer appears to be the case.

The epidemiologic data having   established a  sound correlation between obesity and risk of atrial fibrillation , the electrophysiologic (EP) cardiologists  began to speculate on possible mechanistic explanations. These so far have included activation of pro-fibrotic pathways,atrial fibrosis, abnormal connexin, ( gap junction proteins necessary for heart cell action potential propagation) diastolic dysfunction , paracrine effect due to proximity of epicardial fat to myocytes,  and more recently  detailed scrutiny of  the role or roles  of epicardial fat to which has been assigned the ironic designation, of  EAT (epicardial adipose tissue) in deleterious remodeling of the left atrium.

At least as early as 2003 cardiac fat  acting like an endocrine organ was identified as a source of inflammatory cytokines ( Il-6,TNF-alpha, etc) that could  possibly promote coronary artery disease. Mazurek et al (2) found higher levels of inflammatory cytokines in patients with significant CAD.

Now EAT is accused of playing a role in the genesis of AF.

Dr, Mahajan and co-workers from Australia  studied 27 obese patients and 27 non obese patients who underwent AF ablation for AF. The obese groups demonstrated evidence of electroanatomical remodeling (global reduction in conduction velocity and increased electrogram fractionation) .The obese group had increased EAT and low atrial voltage in the posterior aspect of the left  atrium adjacent to EAT.

Author quotes:

" obesity related conduction abnormalities were most prominent in the posterior left atrium which was in close contact with the epicardial fat. "

"Obesity results in expansion of EAT and marked electroanatomical remodeling of the left atrium,creating a substrate for AF"



1)Mahajan, R etl al Electroanatomical Remodeling of the atria in Obesity. Impact of adjacent epicardial Fat.JACC, clinical electrophysiology vol 4, no 12, 2018 ,p 1531.

2)Mazurk, T et al Human Epicardial adipose tissue is a source of inflammatory mediators.
Circulation 2003, 108 r122-128

Did a third randomized trial for PSA screening reconcile the conflict betwen the first two?

Did the third RCT settle the issue of the efficacy of PSA screening for prostate disease?  The short answer is no - that settling purportedly was   achieved by another statistical analysis. ( see reference # 2 for that) at least for a while .

There are now three large RCTs (1) that have addressed the subject.

1) the PLCO
2) The ERSPC
3) the Cluster Randomized Trial of PSA testing for Prostate Cancer.

Only the ERSPC demonstrated reduction in cancer in an "invitation to screening"  with PSA setting.

So did the two out three being negative settle the issue? Not even close.

In 2012, faced with two conflicting RCTs the USPSTF decided to recommend against screening with PSA.Then a third RCT was completed showing no difference in mortality in the PSA screened group.

So if the score was 2 to 1 showing no benefit for PSA screening why did the USPSTF recant and return to their recommendation of "shared decision making" in 2018?

 The answer seems to be that Tsodikov from the University of Michigan ( and 21 other authors from various institutions)   did some adroit statistical footwork (2) in an effort to reconcile the disparate findings. Their work appears successful with the conclusion
being that when the proper type analysis is done (taking into account mean lead time) both the PLCO and the ERSPC both demonstrated approximately the same decrease in mortality with PSA screening.
Note the original analysis did not show a benefit to screening .

So now the score is two RCTs in favor of screening with one against and the current USPSTF recommendation is for shared decision making.


1)A blueprint for cancer screening and early detection :Advanced screening's contribution to cancer control. Wender RC et al . Ca,A Cancer Journal for Clinicians, Vol 49, no 1 Jan/Feb 2019 ( This is an excellent review of screening for cancer detection in average risk, asymptomatic adults including breast,cervix,colorectal,endometrial,lung and prostate.}


2)Tsodikov, A Reconciling the effects of screening on prostate cancer mortrality in the ERSPC and PLCO trials, An Intern Med. 2018, 168 608


"Life is short,art long,opportunity fleeting, experience treacherous,judgment difficult."Hippocrates.

Left bundle branch block -a really big deal part 2

Left bundle branch block (LBBB) is associated with a contraction pattern(s), that are dyssynchronous in regard to the pattern of left venricular (LV) relaxation and contraction.

The first "big deal " I commented on was the observation that the ventricular dyssynchrony associated with LBBB per se can lead to heart failure. See here.

The next big deal is that the pattern of ventricular dyssynchrony typical of "true" LBBB is determinative of a favorable clinical response to CRT and the presence of a LBBB EKG pattern does not necessary indicate a underlying LBBB dyssynchronous pattern.


Risum et al (1) list 3 criteria for the typical contraction pattern of a "true"LBBB
(these apply to description of a longitudinal stain curve in a 4 chamber 2-D strain echocardiogram)

1)early shortening of one or more segment in the ventricular septal wall and early stretching in one or more segments in the lateral wall
2)early septal peak shortening
3)lateral wall peak shortening after aortic valve closure

The early shortening of the septum is recognizable on standard echocardiography and referred to as "septal flash". "Apical rocking" is another echo finding in which there is a rocking motion  of the LV apical  myocardium perpendicular to the long axis. These two findings seem to be the findings on routine echo exams that correspond at least to some degree  (possibly large degree) to the Risum's criteria from strain echocardiography and  perhaps share to some degree the predictive power as regards outcomes of cardiac resynchronization therapy (CRT).

Those patients with a ekg pattern of LBBB and these findings on strain echo are much more likely to have a favorable clinical response to CRT.

Not all patients with a typical LBBB EkG pattern have what Risum refers to as the typical LBBB contraction pattern which is predictive of likelihood of favorable response. to CRT.This seems to hold true in regard to both the standard criteria for LBBB and the newer Strauss criteria .


Quoting Risum : "It seems reasonable to believe that the main mechanism underlying the differential effect from CRT according to QRS morphology is whether a significant activation delay is present in the LV". ( my underlining)

Question: Does the presence of septal flash and apical rocking predict likelihood of success with CRT as good or better than Risum's criteria? Have the two set of criteria been directly compared? While I could find no direct comparison ,Stankovic et al (2) published data that indicated apical rock and septal flash could predict reverse remodeling with a sensitivity of 84 % and 79% and the absence of both was associated with unfavorable long term survival.

Bottom line from Risum's work is that a patient may have EKG criteria for LBBB  (either the standard criteria or the new criteria proposed by Strauss) and not have the mechanical dyssynchrony pattern described by Risum  and not respond well to RCT.

So is the evidence strong enough to recommend pre-implantation 2d strain echo and not proceed with Bi-V pacing if the Risum criteria are not met? Is the absence of apical rock and septal flash reason to not proceed with Bi-v (or His Bundle) implantation?



1) Risum , N Identification of typical left bundle branch block contraction by strain echocardiography is additive electrocariography in prediction of long-term outcome after cardiac resynchronization
J Amer Coll of cardiology, 2015, vol 66, no. 631-641

2)Stankovic, I Relationship of visually assessed apical rocking and septal flah and long term survival following cardiac resynchronization therapy (PREDICT-CRT) Eur Heart J Cardiovasc Imaging. 2016,Mar 17 (3)262-9

addendum 1/30/19 reference to the Stankovic paper added

Once I thought I knew how to advise people how to eat to reduce heart disease risk , Now....

Read this recent brief overview of diet and fats and carbs and and cholesterol levels  and heart disease risk and see if you would presume to advise patients on how to eat. I am glad that I am out of that business.

I have written several times on medical hubris . In light of what we think we "know" now and what I advised ten years ago,I think "who is without sin....." I believed I had the answer while having answers was little more than parroting the recommendations of boards and organizations.

You have to remember the lawyer's classic query "Doctor, where you wrong then or are you wrong now/"

Neither the pre-operative beta blocker debacle nor the post menopausal use of estrogen and progesterone missteps seem to be a teaching moment for the population medicine devotees. The pop med folks , as explicated here would presume to take funds away from the treatment of some to fund preventive program to others which would "after a few generations" bring about a utilitarian gain by some metric even as some might suffer now.

At the time of this writing serious doubt has been cast on the previously widely disseminated advice about how to eat to avoid heart disease and who should take aspirin for primary prevention of coronary artery disease and who , if anyone, shovel be screened to detect low vitamin D levels, just to name a few of the ever changing array of medical recommendation to prevent disease and death. 

The internist who once upon a time was thought to be the physician trained to diagnose and treat complex complicated medical conditions has to extent  that she is now a ambulist ( at least those who are not now hospitalists) sends her time in part giving advice about how to prevent disease. How to eat,how often to get a cervical cancer screening test or a colonoscopy , who should take statins of aspirin or vitamins  and how much to exercise. For this you did not need to study four years in medical school and then three of more years of internal medicine training.You just need to subscribe to a service ( an app on your IPAD) to keep you up to date on the latest, and every changing, recommendation of various panels.

"Some people do not deserve health care reform?what would Maimonides have said?

The notion of someone "not deserving medical care reform" has appeared at least twice in writings by physicians. KevinMD taked about it here as he called attention to a commentary by Dr Edwin Leap. Dr.Leap is a long time medical blogger and ER physician and submitted this essay to an online version of a newspaper.

My first cursory reading of the essay and KevinMD's comments I erroneously read it to say " "Do some people not deserve medical care"


Sometime ago I wrote about a wonderful essay by Dr. Lawrence J. Hergoff published in JAMA which seems to address this line of thought.


Near the end of his current manuscript he quotes part of the Oath of Maimonides:

"May I never see in the patients anything but a fellow creature in pain."
I added:

Not as someone who deserves his dyspnea because of cigarette use defying years of advice to quit, not as someone whose ascites is his just due from profligate use of alcohol, not as someone who should not be in this country at all, not as someone who would not be having the myocardial infarction at all if he had done what his doctors told him to do and not as someone who is taking "scarce medical resources" from someone who deserves them more or for whom the treatment could be more cost effective but as a fellow human whose is in need of what physicians spent so many years of their lives preparing themselves to be able to offer.

The oath ( Maimonides) should remind us that being face to face with a fellow human in need

..makes judgment beyond the biomedical not only unnecessary but inappropriate.

Comments on the "Extreme Exercise Hypothesis"

Dr. THM Eijsvogels  from the Netherlands has written extensively about the relationship between endurance exercise levels and various cardiovascular outcomes and findings.

His  recent (1) review with an annotated references list  is available in full text on line.

Maybe the first question should be "what do you  mean "extreme'?

U.S. National and WHO guidelines  recommend 250 minutes of moderate exercise per week or 125 minutes of vigorous ( greater than 7 METS) per week based on in part a well established  reduction in cardiovascular mortality and morbidity as well as numerous other health benefits. However ,US guidelines also state that exercise above that levels is associated with added benefits. But how far "above" should one go. Can you go too far?

Is there a U-shaped curve when you plot health risk of the Y axis and exercise training volume on the x axis? If so, can the inflection point be defined?

Arem (2015) combined data from six prospective population based cohorts ( 661,137 individuals).Maximal all-cause mortality risk reduction was noted at exercise level of 3-5 times current recommendations and even  those exercising at 10 times current recommendation had a lower mortality risk  ( HR 0.69, 95% CI 0.59-0.78). But at the highest level the degree of risk reduction was  less than that achieved by lower exercise levels,

Ten times would be 25 hours ( one full day) of moderate exercise per week,I suggest very few exercise at that level while many preparing for a marathon would likely exercise  as much as 7 or 8 hours a week (3-5 the recommend levels). Olympic rowers might exercise as much as 17-18 hours a week .The relatively few exercisers at the highest volume make the confidence intervals for HR estimation at that exercise level so large as to not be reliable or useful.

Eijsvogels summarizes the quest for "what do mean by extreme" with this understatement:

" Based on limited current evidence and numerous potential confounders, it is difficult to delineate an upper limit for the for the benefits of physical activity at this time."

So there is no epidemiologic support for a U shaped relationship between exercise volume and health risk at least as measuring all-cause mortality. But what about certain medical conditions that have been reported to be increased in long time endurance athletes at levels said to be higher than those who exercise less.

The usual suspects include 1) atrial fibrillation 2)cardiac fibrosis 3)coronary artery calcifications.

I have commented on atrial fibrillation before ( see here) and will likely have more to say later and have blogged about the coronary  calcification paradox before( see here).

Cardiac or myocardial fibrosis (MF) is detected by cardiac MRI imaging with injection of gadolinium  and  is referred to as late gadolinium enhancement (LGE).There is a recognized pattern of LGE designating the  localized fibrosis following a heart attack. The  LGE pattern at issue in endurance athletes is something different-, i.e. a non-ischemic pattern. .

Van de Schoor et al did a systematic Pub Med search (2) and identified 65 athletes with MR imaging. A subgroup (30 subjects) were identified in an MRI study of 509 athletes.

The most frequent pattern was that located near the interventricular septum  and right ventricular insertion points. The significance of this type of myocardial fibrosis is unclear.

Levine (3) et al have suggested that LGE in endurance athletes may not represent irreversible fibrosis and note that a similar pattern of LGE at the insertion points is seen in hypertrophic cardiomyopathy and also pulmonary hypertension.

Chan et al (4) described the histopathology in patients with hypertrophic cardiomyopathy (HCM). In a multi institutional study of 1293 HCM 10% demonstrated small areas of LGE in the area of  ventricular insertion into the ventricular septum. Biopsies showed " greatly expanded extracellular space" with intestinal fibrosis and disorganized myocyte patterns." The authors emphasized the pattern was not that of myocyte death and replacement fibrosis.

Perhaps a similar histologic pattern would be found in the endurance athletes but to my knowledge that information is not available.

LGE has been reported in participants in various sports , the first case was a soccer player. Its significance and underlying mechanism  ( repetitive microtrauma, transient pulmonary artery pressure over load ??) are  not known.

 I have to agree with Eijsvogels' summary statement :  )"There is limited evidence that supports the "extreme exercise hypothesis",the most compelling relating to the increased risk of atrial fibrillation at high volume of exercise. 2) cardiac abnormalities may be present in a small proportion of the most active veteran athletes …"






1)Eijsvogels, TMH, er al The "Extreme Exercise Hypothesis:Recent findings and cardiovascular
health Implications. C"urr Teat Options Cardio Med 2018 20:84

2)Van de Schoor, F ,et all Myocardial Fibrosis in athletes . Mayo Clin Proc 2016,2016

3)Abdullah, Sm Lifelong Physical Activity regardless of does is not associated with myocardial
fibrosis. Circ Cardiovas Imaging. 2016 9,:e005511 (ful text)

4)Chan R, et al Significance of late gadolinium enhancement at right ventricular attachment to ventricular septum in patients with hypertrophic cardiomyopathy. Am J cardiol. 2015:116 436

The concept of medical commons is a bogus and dangerous concept

A fundamental concept of the various types of egalitarianism is. neither coherent,correct and operationally meaningful. .. That concept is : Individually possessed  resources or assets should be considered as part of a collective pool owned by everyone and that all have an equal right to some share of the pool.

In regard to a private property system the rights of the owner in general terms are clear. The owner has the right to use his property,exclude others from us of the property and dispose of the property through sale,gift or inheritance.

 In contrast , the rights are in a common ownership system are vague and indeterminate. Feser said it is not clear how one can be said to "own" something if no one in principle is excluded from making a claim on that something.

Even a  cursory survey of the twentieth century reveals how tragic and unsuccessful were attempts to build a society based on the notion of common ownership and the abolition of private property. The Bolshevik revolution promised peace,freedom ,equality and prosperity and delivered mass murder and starvation.Communist China's attempt in that regard were no better .The dramatic nighttime photograph of the Korean peninsula showing darkness in the north and countless points of light in the south tells the story of the difference between the two systems of ownership..

Yet the movement to consider medical or health care resources as a central pool or a medical commons has had surprisingly wide acceptance in certain medical organizations and medical academia and among health care planners and policy wonks.

Even though the concept of a collective pool of individually possessed resources is basically void of meaningful operational content a derivative metaphor-that of the physician as a steward of the mythical medical resources-has been promulgated and to some a surprising degree accepted and has become part of a major  and growing effort to control medical care and has become part of the discourse about health care policy.

The rules by which a collective of healthcare resources  would be allocated are not defined, but  those who advocate the physician as steward of these resources have several things in mind to make the metaphor operationally meaningful, the most important of which is the purported ethical requirement of physicians to adhere to guidelines which in their most at least superficially justifiable  analytical form are based on a cost benefit analysis and in their least evidence based form , expert opinion.

Cost effective analysis has been smuggled into the professionalism package in the trojan horse of social justice. This is bogus as well. The utilitarian mantra of the greatest good for the greatest number is not necessarily a part of the concept of social justice.The basis of social justice is equal respect for all humans while utilitarians would favor policies that benefit the aggregate though some individual may loose. The prominent egalitarian John Rawls rejected utilitarian allocations because they ignored the separateness of individuals and in his mythical behind- the- veil contract he believed that individuals would not sign up for a society that would sacrifice them for some aggregate benefit.

High value? Fuzzy concept? who gets to decide?

"Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry." From a blog commentary by Dr. Robert Centor. Yes, we should all worry.

Value and quality have be become buzz words-  to be blended into "value statements" and purported goals .

Classical economists ' notion of value as something imparted into a good by the labor expended in its production was overturned by economists in the late 1800s when Menger and others introduced the idea of  marginal subjective value. The value of a good or service was subjective,that is in the eye of the beholder, and was made "at the margin".The value of the tenth piece of apple pie is less to a person than is the value of the first piece. Great effort and artistic skill might be expended in the production of an artistically beautiful pogo stick but labeling it a high value product would not  bring about large sales of such a product. Few potential consumers would value such a product.

Marx 's labor theory of value is  resurrected in the payment system  for medicare "The doc fix" carried that archaic misconception  further. The Medicare payment scheme contains elements likely to be admired by the old time Soviet Union central planners.

Third party payers embrace the notion of high value medical care . The words quality and high value are  loose, vague and indeterminate  but seem to have considerable rhetorical value . They are found to a degree making them worthless in myriads of value and missions statements of various organizations whose actual activities and goals have nothing to do with those statements.

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

What happens to your heart in you train really hard for a year or two may depend on your age

First -what happened to the hearts of young men and women who trained intensively for one year in preparation for a marathon.See below for changes noted in older subjects.

Dr.Benjamin Levine (1) and colleagues at the Institute for Exercise and the Environment performed extensive physiologic studies on 12   subjects ( aged 29 +/- 6 years) and provided valuable insight into the functional and structural change in their hearts over  one year.

The training program was intensive and progressive and was divided into four 3 months periods or segments. The third quarter included 2 hour long runs and 4 th quarter involved 7 -9 hours per week  with 3 hour long runs and interval training.

The cardiovascular system of the trained endurance athlete differs in a number of ways from the untrained person.These include:

1.increased red blood cell mass and blood volume

2.increased numbers of mitochondria and capillaries in leg muscles.

3.lower peripheral arterial resistance

4.lower systolic and diastolic blood pressure during exercise.

What distinguishes the elite endurance athlete's heart from other equally well trained athletes is the very large stroke volume which in turn depend on a very large end diastolic left ventricular volume (LVEDV). A  very compliant left ventricle is the key (.It may be more accurate to state "compliant heart" as that would include a more easily stretched pericardium facilitating diastolic filling.)

The maximal 0xygen uptake increased from 40.3 =/-1.6 to 48.7  =/-2.5. (The 02 max for elite marathoners is typically 70 to 80 plus).  Maximal stroke volume increased from 98 to 113 ml.

A key finding was that both right and left ventricular mass increased to levels similar to those seen in elite athletes but the LV volume did not change until six months of training. In the first 6 months of training when training did not include significant high intensity training the left ventricle remodeling was concentric and eccentric remodeling ( i.e. increased LV volume) did not occur more intense exercise was part of the regimen.The right ventricle began "eccentric" hypertrophy early on. Question -is the eccentric pattern dependent on the addition of some HIT or interval training in addition to the moderate intensity exercise.

Cardiac catherization data derived measures of LV compliance improved but did not approach those typically observed in elite athletes. The "Starling Curves" which plot pulmonary capillary wedge pressure (PCWP) which is an index of left ventricular filling pressure on the x axis versus stroke volume on the y axis shifted up and to the left suggesting an improvement in left ventricular compliance, i.e a ventricle more easily filled.


Their morphology measurements which  were done by cardiac MR ( generally thought to be more accurate than echocardiographic measurements) did not conform with the Morganroth hypothesis (1975) which stated that endurance exercise lead to eccentric hypertrophy which is a balanced increase in wall thickenss and ventricular volume while strength training leads to concentric hypertrophy with an increase in wall thickness with no significant change in cavity size.

Levine's subjects first had a LV concentric pattern and only after more intense ( volume and intensity) exercise was part of the program did the classic endurance athletes eccentric pattern become evident. A certain level of  intensity of exercise seemed to be necessary for aerobic exercise to cause eccentric hypertrophy. This seems to run contrary to the notion  that endurance exercise is simply a "volume overload event".

Levine's group has also reported on a similar project (2) involving older ( age 68-74) subjects and although their training program was vigorous it was less intense than the young subjects.The 02 max increased on average by 19%,arterial elastance decreased, LV mass increased with no change in the mass volume ratio ( i.e physiologic remodeling) but the Staring curves did not indicate a more compliant left ventricle.So good things happened but improved LV compliance was not one of them.

The third publication (3) in Levine's hat trick involves similar measurements of  heart function and structure in middle age subjects over  a two year period.The details are complex and interested readers can find details in ref 3 which has  entire text without firewall.

The two year training program involved at least 30 minute session of moderate exercise 4-5 times  per week with at least one high intensity exercise session ( the Norwegian 4x4).
The authors were able to show an improvement in compliance using the techniques ( The Starling curves) mentioned above .The data offer the hope that "middle age" is not too late to start .

Levine suggests that sedentary aging effect of the heart has 3 stages; 1) loss of relaxation 2)loss of compliance or stiffening of the myocardium and 3) remodeling.This sedentary aging may predispose  to heart failure with preserved ejection fraction (HFpEF) perhaps when confronted  by another "hit" such as hypertension,obesity,and diabetes. Levine's data suggests that some doable amount of endurance exercise might retard or mitigate the process . (Whether high intensity exercise is a necessary component is still an open question)

t





1) Arbab-Zadeh, A  "cardiac remodeling in  response to 1 year of intensive endurance training.
Circulation 2014, 130 (24) 2152

2)Fujimoto,N Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circ. 2010, 122 (18), 1797

3) Howden EJ et al Reversing the cardiac effects of sedentary aging.A randomized 
trial.Circulation,2018 137; (full text available on line without firewall)

addendum 2/17/19 Comment about pericardium added.